Stressful events may trigger disease processes in many different organ systems, with the cardiovascular system being particularly vulnerable. Five-mo-old male rats had ad libitum (AL) access to food or were deprived of food every other day [intermittent food deprivation (IF)] for 6 mo, during which time their heart rate (HR), blood pressure (BP), physical activity and body temperature were measured by radiotelemetry under nonstress and stress (immobilization or cold-water swim) conditions. IF rats had significantly lower basal HR and BP, and significantly lower increases in HR and BP after exposures to the immobilization and swim stressors. Basal levels of adrenocorticotropic hormone (ACTH) and corticosterone were greater in the IF rats. However, in contrast to large stress-induced increases in ACTH, corticosterone and epinephrine levels in AL rats, increases in these hormones in response to repeated immobilization stress sessions were reduced or absent in IF rats. Nevertheless, the IF rats exhibited robust hypothalamic/pituitary and sympathetic neuroendocrine responses to a different stress (swim). The IF treatment improved glucose metabolism, as indicated by lower basal levels of circulating glucose and insulin, but with maintenance of glucose and insulin responses to stress. We concluded that improvements in cardiovascular risk factors and cardiovascular and neuroendocrine stress adaptation occur in response to IF.